He succeeded to the position of the Emir of Abu Dhabi on November 2004 after the death of his father Zayed bin Sultan Al Nahyan, thereby becoming the President of the federation next day. Although as Crown Prince, he had effectively been acting president earlier since the late 1990s as his father was in ill health. Khalifa is also chairman of Abu Dhabi Investment Authority, which manages over $600 billion in assets. while the Al Nahyan family is believed to have a fortune of $150 billion collectively as a family.[3]

Khalifa was appointed as Ruler's Representative in the Eastern Region of Abu Dhabi (the mayor) and as Head of the Courts Department in Al Ain in 1966, as his father Zayed bin Sultan Al Nahyan became the new ruler of Abu Dhabi. Zayed was the Ruler's Representative in the Eastern Region. A few months later the position was handed to Tahnoun bin Mohammed Al Nahyan.[4]

On 1 February 1969, Sheikh Khalifa was nominated as the Crown Prince of Abu Dhabi, and on the next day he was appointed as the Head of the Abu Dhabi Department of Defense, in which post he oversaw the building up of the Abu Dhabi Defense Force, ADDF, which later became the nucleus of the UAE Armed Forces after 1971.

In May 1976, he became deputy commander of the UAE armed forces, under the President. He also heads the Supreme Petroleum Council in the late 1980s (until today), which enjoys wide powers in energy matters. He was the chairman of the Environmental Research and Wildlife Development Agency, ERWDA.

He succeeded to both posts on 3 November 2004, replacing his father Zayed bin Sultan Al Nahyan, who had died the day before. He had effectively been acting president earlier, since his father was ill during the period prior to his passing.

On 1 December 2005, the President announced that half of the members of the Federal National Council, the closest body the country has to a parliament, will be indirectly elected. However, half of the council's members will still need to be appointed by the leaders of the emirates. The 40-member FNC serves in an advisory capacity. The elections were set to take place in December 2006.

On 4 January 2010, the world's tallest man-made structure, originally known as Burj Dubai, was renamed to Burj Khalifa, in honor of the Sheikh.[6]

Sheikh Khalifa is known for his interest in sports traditional to UAE, chiefly horse and camel racing. He is generally regarded as a pro-Western modernizer. Early in his term, in April 2005, he authorized a 100% salary increase for employees of the state.[citation needed]

In 2010, Khalifa was described in a recent WikiLeaks cable signed by the U.S. ambassador as a "distant and uncharismatic personage."[7]

On 24 January 2014 Sheikh Khalifa suffered a stroke and was reported to have undergone an operation and be in a stable condition,[8] subsequent reports on his health on social media were dismissed as rumours.[9]

Seychellois government records show that since 1995 Sheikh Khalifa has spent $2 million buying up more than 66 acres of land on the Seychelles' main island of Mahé, where his palace is being built.[10] Since 1995 the Seychelles' government has received large aid packages from the UAE; the UAE has pledged more than $130 million in social service and military aid, including patrol boats for the Seychelles' antipiracy efforts. In 2008, the UAE came to the indebted Seychelles government's aid, with a $30 million injection.[10]

Khalifa paid $500,000 for the 29.8-acre site of his palace in 2005, according to the sales document. A Seychelles planning authority initially rejected the palace's building plans, a decision overturned by President James Michel's cabinet.[10] A month after the start of construction of the palace, the national utility company warned that the site's plans posed threats to the water supply. Joel Morgan, the Seychelles' minister of environment, said the government did not tender the land because it wanted it to go to Khalifa. Morgan said "the letter of the law" might not have been followed in the land sale.[10]

On 13 February 2010, the sewage system set up by Ascon, the company building the palace, for construction workers building the palace, overflowed, sending rivers of waste through the region, home to more than 8000 residents.[10] Local government agencies and officials from Khalifa's office responded quickly to the problem, sending in technical experts and engineers. Government officials concluded that Ascon ignored health and building codes for their workers, and fined the company $81,000. Ascon blamed the incident on "unpredicted weather conditions".[10]

Khalifa's presidential office offered to pay $15 million to replace the water-piping system for the mountainside.[10] Government officials and residents say Ascon has offered to pay roughly $8,000 to each of the 360 households that the government says have been affected by the pollution.[10]

The largest grant in the center's history will support construction of a state-of-the-art facility to house the Khalifa bin Zayed Al Nahyan Specialty Institute for Cancer Diagnosis and the Ahmed bin Zayed Al Nahyan Pancreatic Cancer Center.[citation needed] The grant also will fund a number of annual fellowships and will be used to endow an oncology chair named after Sheikh Zayed bin Sultan Al Nahyan, a cancer research chair named after Sheikh Khalifa University, and a scientific and medical research chair named after Mohammed bin Zayed Al Nahyan.[citation needed]

Speaking at a signing ceremony, M. D. Anderson Center president John Mendelsohn said that the funding will be channeled into research programs dedicated to discovering new and more effective ways of diagnosing and treating cancer.[citation needed]

On 12 January 2011, the UAE Pakistan Assistance Program was launched in order to help and provide assistance to Pakistan and mitigate the impact of floods by redeveloping infrastructure, according to the directives of Khalifa Bin Zayed Al Nahyan, the President of the United Arab Emirates. The UAE PAP has worked along a comprehensive redevelopment plan that takes into account the harsh geography and the rough weather conditions of the region while focusing on four main areas of social redevelopment: health, education, water and infrastructure. The Program has taken some vital steps to ease the pain and suffering that the people of Swat have become accustomed to as it provided for the construction and rehabilitation of two bridges, 52 schools and 7 hospitals, as well as the implementation of 64 water supply schemes.Uae Pakistan Assistance Program